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Evaluation of Wuchereria bancrofti GST as a vaccine candidate for lymphatic filariasis.

ABSTRACT: Lymphatic filarial parasites survive within the lymphatic vessels for years despite the complex immune environment surrounding them. Parasites possibly accomplish this by adopting various immunomodulatory strategies, which include release of glutathione-S-transferases (GSTs) that counteract the oxidative free radicals produced by the host. Since GSTs produced by parasites appear to be critical for the survival of parasites in the host, several studies evaluated the potential of parasite GSTs as vaccine candidates especially against schistosomiasis, fascioliasis and Seteria cervi. However, vaccine potential of GSTs of lymphatic filarial parasites has not been evaluated before.In the present study, the GST gene was cloned from the third stage larval (L3) cDNA libraries of Wuchereria bancrofti, and recombinant GST (WbGST) was expressed and purified. Serum samples from individuals living in an endemic area were analyzed for their reactivity with rWbGST. These findings showed that sera from endemic normal individuals (EN) carry significant levels of anti-WbGST IgG antibodies compared to subjects who are microfilaraemic (Mf) or show symptoms of clinical pathology (CP). Isotype analysis of the anti-WbGST IgG antibodies showed a predominance of IgG1 and IgG3 antibodies in EN individuals. Subsequent functional analysis of the rWbGST showed that the rWbGST protein retained the enzymatic activity of GST and the antibodies in EN sera could inhibit this enzymatic activity. Similar results were obtained when anti-rWbGST antibodies raised in mice were used in the neutralization assay. Brugia malayi GST and WbGST show significant sequence similarity. Therefore, to evaluate the vaccine potential of rWbGST, we used B. malayi L3 as challenge parasites. Vaccine potential of rWbGST was initially evaluated by confirming the role of human and mice WbGST antibodies in an antibody dependent cellular cytotoxicity (ADCC) assay. Subsequent vaccination studies in a jird model showed that approximately 61% protection could be achieved against a B. malayi L3 challenge infection in jirds immunized with rWbGST.Results of this study show that rWbGST is a potential vaccine candidate against lymphatic filariasis. Nearly 61% protection can be achieved against a B. malayi challenge infection in a jird model. The study also showed that the WbGST protein retained the enzymatic activity of GST and this enzymatic activity appears to be critical for the survival of the parasite in the host.

SUBMITTER: Veerapathran A

PROVIDER: S-EPMC2685978 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Evaluation of Wuchereria bancrofti GST as a vaccine candidate for lymphatic filariasis.

Veerapathran Anandharaman A Dakshinamoorthy Gajalakshmi G Gnanasekar Munirathinam M Reddy Maryada Venkata Rami MV Kalyanasundaram Ramaswamy R

PLoS neglected tropical diseases 20090609 6

<h4>Background</h4>Lymphatic filarial parasites survive within the lymphatic vessels for years despite the complex immune environment surrounding them. Parasites possibly accomplish this by adopting various immunomodulatory strategies, which include release of glutathione-S-transferases (GSTs) that counteract the oxidative free radicals produced by the host. Since GSTs produced by parasites appear to be critical for the survival of parasites in the host, several studies evaluated the potential o ...[more]

PMID: 19513102

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Project description:BACKGROUND:Lymphatic filariasis (LF) is widely endemic in Côte d'Ivoire, and elimination as public health problem (EPHP) is based on annual mass drug administration (MDA) using ivermectin and albendazole. To guide EPHP efforts, we evaluated Wuchereria bancrofti infection indices among humans, and mosquito vectors after four rounds of MDA in four cross-border health districts of Côte d'Ivoire. METHODOLOGY:We monitored people and mosquitoes for W. bancrofti infections in the cross-border health districts of Aboisso, Bloléquin, Odienné and Ouangolodougou, Côte d'Ivoire. W. bancrofti circulating filarial antigen (CFA) was identified using filariasis test strips, and antigen-positive individuals were screened for microfilaremia. Moreover, filarial mosquito vectors were sampled using window exit traps and pyrethrum sprays, and identified morphologically at species level. Anopheles gambiae s.l. and Culex quinquefasciatus females were analyzed for W. bancrofti infection using polymerase chain reaction (PCR) technique. PRINCIPAL FINDINGS:Overall, we found a substantial decline in W. bancrofti infection indices after four rounds of MDA compared to pre-MDA baseline data. CFA prevalence fell from 3.38-5.50% during pre-MDA to 0.00-1.53% after MDA interventions. No subjects had detectable levels of CFA in Ouangolodougou. Moreover, post-MDA CFA prevalence was very low, and below the 1% elimination threshold in Aboisso (0.19%) and Odienné (0.49%). Conversely, CFA prevalence remained above 1% in Bloléquin (1.53%). W. bancrofti microfilariae (Mf) were not found in Aboisso, Bloléquin, and Ouangolodougou, except for Odienné with low prevalence (0.16%; n = 613) and microfilaremia of 32.0 Mf/mL. No An. gambiae s.l. and Cx. quinquefasciatus pools were infected with W. bancrofti in Bloléquin and Ouangolodougou, while they exhibited low infection rates in Aboisso (1% and 0.07%), and Odienné (0.08% and 0.08%), respectively. CONCLUSIONS:In cross-border areas of Côte d'Ivoire, LF infection indices in humans and mosquito vectors substantially declined after four rounds of MDA. CFA prevalence fell under the World Health Organization (WHO)-established threshold (1%) in Aboisso, Ouangolodougou and Odienné. Moreover, W. bancrofti prevalence in mosquitoes was lower than WHO-established threshold (2%) in all areas. This might suggest the interruption of W. bancrofti transmission, and possible MDA cessation. However, a formal transmission assessment survey (TAS) and molecular xenomonitoring in mosquito vectors should be implemented before eventual MDA cessation. However, MDA should pursue in Bloléquin where W. bancrofti infection prevalence remained above 1%. Our results provided important ramifications for LF control efforts towards EPHP in Côte d'Ivoire.

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Evaluation of Wuchereria bancrofti GST as a vaccine candidate for lymphatic filariasis.

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Evaluation of Wuchereria bancrofti GST as a vaccine candidate for lymphatic filariasis.

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